Within the context of a continuing broad interest in various factors influencing leukocyte proliferation and differentiation, specific studies will attempt to: (1)\continue to explore mechanisms involved in the regulation of human lymphocyte proliferation in short-term cultures; and (2)\further delineate the role of cytogenetic abnormalities (both the specific chromosomes involved and the types of aberrations) in the initiation and subsequent evolution of human preleukemic disorders and atypical acute leukemia. For the studies of normal lymphocytes, (1)\we will emphasize the role of soluble growth factors in both mitogen-stimulated and antigen-stimulated cultures, and particularly stimulatory and inhibitory factors produced by macrophages. These investigations will utilize macrophage-depleted cultures of normal human lymphocytes exposed to macrophage-derived supernatants in combination with different mitogens and antigens. For the chromosome studies, (2)\we will extend and broaden an existing preleukemia and pursue a similar study on cases of poorly differentiated adult acute leukemia which do not fit present standard classification. These investigations will not only have clinical applications but will also extend our understanding of the significance of genetic alterations in the initiation and evolution of human neoplastic cell populations.